Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Abstract

Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the ''drivers'' of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.

ALDH1 in Combination with CD44 as Putative Cancer Stem Cell Markers are Correlated with Poor Prognosis in Urothelial Carcinoma of the Urinary Bladder

“…CD44, a specific receptor for hyaluronic acid and adhesion/homing molecule (Naor et al, 2008;Jaggupilli and Elkord, 2012), is a multifunctional class I transmembrane glycoprotein expressed in almost all normal and cancer cells (Naor et al, 2008;Jaggupilli and Elkord, 2012). In several previous studies, CD44 individually or in combination with other putative CSC markers has been applied to isolate CSCs in various solid tumors including breast (Al-Hajj et al, 2003), prostate, pancreas (Immervoll et al, 2011), ovarian, colorectal (Wielenga et al, 1993;Woodman et al, 1996;Choi et al, 2009), head and neck (Satpute et al, 2013) and bladder cancers (Yang and Chang, 2008;Chan et al, 2009;Slomiany et al, 2009;Lee et al, 2010;Su et al, 2010;Jaggupilli and Elkord, 2012). Both in vitro and in vivo studies have shown that CD44+ bladder cancer cells have higher tumorigenic potential compared to CD44-bladder cancer cells; whereas they have lower tumorigenic potential compared to ALDH1A1+ cells .…”

Co-Expression of Putative Cancer Stem Cell Markers, CD133 and Nestin, in Skin Tumors

“…They are similar to stem cells and are capable of both self-renewal and differentiation into all of the cells within a tumor (Siclari and Qin, 2010;Rangwala et al, 2011). CSCs have been identified in a number of cancers including acute myeloid leukaemia (AML) (Bonnet and Dick, 1997;Passegue et al, 2003), glioblastoma (Singh et al, 2003), breast (Al-Hajj et al, 2003;Ponti et al, 2005), lung (Kim et al, 2005), prostate (Collins et al, 2005), ovarian (Bapat et al, 2005), gastric (Houghton et al, 2004), esophagous ( Li et al, 2013 ), Head and Neck SCC (Satpute et al, 2013) and skin cancers (Frank et al, 2005;Monzani et al, 2007). Different markers have been identified to be expressed on melanoma stem cells (Quintana et al, 2010;Shakhova and Sommer, 2013) comprising CD20 (Fang et al, 2005) and ABC transporter family members such as MDR1, ABCG2 and ABCB5 (Frank et al, 2003;Frank et al, 2005;Monzani et al, 2007;Keshet et al, 2008;Schatton et al, 2008), CD271 (Boiko et al, 2010;Civenni et al, 2011), CD44 (Fernandez-Figueras et al, 1996, CD133 (Klein et al, 2006) and Nestin (Piras et al, 2010;Fusi et al, 2011).…”

Influence of CD133+ expression on patients' survival and resistance of CD133+ cells to anti-tumor reagents in gastric cancer

“…It is, therefore, rational that human myeloblastic leukemia derives from stem cells [6]. TICs with CD133 + expression have been subsequently identified in various solid tumors, such as breast cancer, brain tumour, prostate cancer, malignant melanoma, colon cancer, liver cancer, pancreatic cancer and head and neck squamous cell carcinoma, though CD133 + cancerous cells have not been classified as cancer stem cells of stomach until now [7][8][9][10][11][12][13][14].…”